The present invention relates to a process for the preparation of optically active cyanohydrins of high optical purity through enzymatic reactions of oxo compounds with hydrocyanic acid in the presence of oxynitrilase.
Optically active cyanohydrins produced by oxynitrilase catalysed addition of HCN to aldehydes or ketones, e.g., derivatives of m-phenoxybenzaldehyde and substituted analogues, are employed as components for the synthesis of photostable pyrethroids.
They are also used for the synthesis of optically active .alpha.-hydroxycarboxylic acids. The latter are in turn employed as feedstuff additives or for obtaining pharmaceutically active compounds, vitamins and liquid crystals.
According to Effenberger et al., Angew. Chem., 95 (No.1), 50 (1983), these optically active .alpha.-hydroxycarboxylic acids can advantageously be converted into optically active N-substituted .alpha.-amino acids, which are otherwise difficult to prepare.
Optically active cyanohydrins likewise provide easy access to optically active .alpha.-amino alcohols and further optically active compounds which can be derived therefrom and are important in the synthesis of biologically active compounds.
German Patent 1,300,111 discloses a process for the preparation of optically active (R)-cyanohydrins in which aldehydes are reacted with hydrocyanic acid in the presence of oxynitrilase. In this known process, the reaction is carried out in an aqueous or aqueous/alcoholic (50 % v/v) reaction medium at a pH of 5.4 (or 4.8 to 5.4; see Becker et al., J. Am. Chem Soc., 1966, 4299), i.e. just below the optimum pH for the enzyme activity, which is between 5.6 and 6. However, the optical purity of the (R)-cyanohydrins produced by this process exhibited some problems.
Effenberger et al., Angew. Chem. 99, 491-2 (1987), investigated the enzymatic formation of cyanohydrins in aqueous/alcoholic systems with variation of the pH, temperature and concentration, with respect to providing optimum suppression of the chemical addition of hydrocyanic acid to the aldehyde group, which accompanies and competes with the enzyme-catalyzed addition and results in racemates. Since it was not possible to produce satisfactory optimization in this way, Effenberger et al. proposed to suppress the chemical reaction by using organic, water-immiscible solvents. In particular, the process was carried out using ethyl acetate and using support-immobilized (R)-oxynitrilase. In this way, products of high optical purity were obtained, but the reaction in an organic medium means a certain technical obstacle, in particular since the activity and stability of the enzyme are reduced in this medium.
A need therefore continues to exist for a method of synthesizing optically active cynohydrins of high optical purity without the disadvantages of the prior art methods.